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Background

Gastroesophageal reflux disease (GERD), defined as weekly heartburn and/or acid regurgitation,
is one of the most common health conditions affecting older Americans. Direct costs attributable to GERD
were estimated to be $10 billion in the United States in 2000.

Some patients have frequent, severe symptoms requiring long-term regular use of
antireflux medications. For these patients, who have chronic GERD, most authorities
consider the goals of therapy to be improvement in symptoms and quality of life, healing of and
maintenance of healed erosive esophagitis, and prevention of complications (such as Barrett's esophagus,
esophageal stricture formation, or esophageal adenocarcinoma). However, there remains considerable
uncertainty regarding how these objectives should be achieved.

Among patients treated medically, several approaches are used, depending in part upon the
severity of symptoms and clinical response. These include intermittent, periodic, or continuous use of
prescription or over-the-counter medications, especially histamine type 2 receptor antagonists (H2RAs)
and proton pump inhibitors (PPIs).

The availability of surgery (fundoplication) and, more recently, endoscopic treatments has
further complicated management strategies. While surgery has been considered to provide an alternative
to permanent use of antisecretory medications, long-term followup of a landmark randomized controlled
trial comparing medications with surgery found that approximately two-thirds of surgically treated
patients still required regular antireflux medications. Furthermore, while advocates of surgery
continue to suggest that it might be more effective than medical therapy for prevention of Barrett's
esophagus and esophageal cancer, evidence supporting this assertion has been inconclusive.

A challenge in treating GERD is that neither improvement in symptoms nor reduction in the need
for antisecretory medications has consistently correlated with objective measures such as normalization
of esophageal pH exposure or healing of esophagitis. The endoscopic approaches, in particular, have
drawn into focus the disparities that can exist among various objectives in treating GERD.

This report examines alternatives for managing the chronic symptoms of uncomplicated GERD in
patients who may require long-term treatment. It summarizes the available evidence comparing the
efficacy and safety of medical, surgical, and endoscopic interventions in the treatment of chronic
GERD, particularly after long-term followup. Questions addressed in this report are:

What is the evidence of the comparative effectiveness of medical, surgical, and endoscopic
treatments for improving objective and subjective outcomes in patients with chronic GERD?

Is there evidence that effectiveness of medical, surgical, and endoscopic treatments varies for
specific patient subgroups?

What are the short- and long-term adverse effects associated with specific medical, surgical,
and endoscopic therapies for GERD?

Conclusions

Comparison of medical treatments with surgery

Medical therapy with PPIs and surgery (fundoplication) appeared to be similarly effective for
improving symptoms and decreasing esophageal acid exposure. However, only a few studies directly
compared these approaches and the total number of patients studied was small.

In the studies reviewed for this report, from 10 percent to 65 percent of surgical patients
still required medications.

The body of evidence supporting the above conclusion was based on three head-to-head comparative
trials. The studies had methodological flaws making them susceptible to some bias, but not sufficient
to invalidate the results (Grade B).

The limited data available did not support a significant benefit of fundoplication compared
with medical therapy for preventing Barrett's esophagus or esophageal adenocarcinoma.

Comparison of surgery with endoscopic procedures

Of the three nonrandomized studies that compared an endoscopic procedure with laparoscopic
fundoplication in patients with GERD documented by pH or endoscopy, the longest followup was 8 months,
and all three studies had significant bias that may invalidate the results (Grade C).

Two studies reported that more patients treated with laparoscopic fundoplication were
satisfied with their results compared with those who had EndoCinchTM. One of these studies and a
study of StrettaÒ also found less need for PPIs in patients who had fundoplication.

Comparison of medical treatments with endoscopic procedures

There was no head-to-head comparison of medical treatments with endoscopic treatments.

Comparison of medical treatments (between classes and within class)

PPIs were superior to H2RAs in resolution of GERD symptoms at 4 weeks and healing of
esophagitis at 8 weeks.

The above conclusion was based on three recent meta-analyses of randomized controlled
trials comparing one medication to another. These analyses had minimal bias and their results are
considered valid (Grade A).

There was no difference between omeprazole, lansoprazole, pantoprazole, and rabeprazole for
relief of symptoms at 8 weeks.

No significant difference was found in the comparisons of esomeprazole 40 mg with
lansoprazole 30 mg or pantoprazole 40 mg for relief of symptoms at 4 weeks. Similarly, there was no
difference in the comparison of esomeprazole 20 mg with omeprazole 20 mg in relief of symptoms
at 4 weeks. When esomeprazole 40 mg was compared with omeprazole 20 mg, there was a significant
difference in favor of esomeprazole for relief of symptoms at 4 weeks.

For maintenance medical treatment of 6 months to 1 year, PPIs taken at a standard dose
(as suggested by the manufacturers' prescribing information) were more effective than those taken at a
lower dose (usually one-half of the standard dose) in preventing relapse of symptoms.

Comparison of surgical techniques

Laparoscopic fundoplication was as effective as open fundoplication for relieving heartburn and
regurgitation, improving quality of life, and decreasing use of antisecretory medications. Almost 90
percent of patients who were followed for 5 or more years in both surgical arms reported improvement in
symptoms.

The above conclusion was based on one fair-quality (Grade B) randomized controlled trial and one
poor-quality (Grade C) nonrandomized study.

Comparison of endoscopic treatment with sham

Compared to sham, StrettaTM was more effective in improving symptoms of reflux and improving quality
of life at 6 months and was associated with a decrease in the need for antisecretory medications.
Improvement of esophageal pH exposure compared with sham could not be demonstrated for
StrettaTM.

This one study on StrettaTM versus sham had a small number of patients and short
duration of followup (Grade B).

Patients on maintenance antireflux medications may have higher rates of esophagitis if they have
any of the following factors: increased severity of esophagitis at baseline (pretreatment), younger age,
and moderate to severe regurgitation.

There is no substantial evidence to support a difference in surgical outcome based on age,
preoperative presence or severity of esophagitis, lower esophageal sphincter incompetence, or esophageal
body hypomotility.

Patients treated surgically who have a history of psychiatric disorders may have worse symptom
and satisfaction outcomes than those without a significant psychiatric history.

The quality of reporting of adverse events and complications was inconsistent across studies.
None of the studies used an acceptable standard or scale for defining severity.

Higher adverse event rates were described for PPIs than for H2RAs or placebo. The most commonly
cited events for PPIs and H2RAs were headache, diarrhea, and abdominal pain.

The most commonly reported complications occurring intraoperatively or within 30 days after open
fundoplication were the need for splenectomy, dysphagia, inability to belch, and inability to vomit. The
most commonly reported complications for laparoscopic procedures were gastric or esophageal injury or
perforation, splenic injury or splenectomy, pneumothorax, bleeding, pneumonia, fever, wound infections,
bloating, and dysphagia. Major complications were generally reported at very low rates.

Frequently reported complications for endoscopic treatments(intraoperatively or within 30 days
after the procedure(included chest or retrosternal pain, gastrointestinal injury, bleeding, and
short-term dysphagia. The frequency and types of complications varied with the different procedures.
Serious complications, including fatalities, have also been described.

Remaining Issues

More studies are needed to inform how patients with GERD should be managed based upon patient
characteristics or response to previous therapy. Additional information is needed to select patients
for specific testing for GERD and to determine how treatment should be guided by the results of testing.

Randomized controlled trials of laparoscopic fundoplication versus PPIs with long-term followup
are needed to ascertain the relative benefits and harms of each approach and whether certain subgroups
are better served with one or the other alternative.

Data on comparative endoscopic treatments with continued (or intensified) use of PPIs are needed
to better understand their efficacy compared to an established standard.

More efficacy and safety data on new endoscopic approaches tested against a sham procedure with
adequate followup are needed.

To minimize patients' exposure to life-long medications, methods need to be developed to identify
patients who do not need long-term antisecretory medications. Long-term studies are needed to assess the
risks associated with acid suppression on the development of pneumonia and enteric infections, and to
assess the consequences of long-term hypergastrinemia.

There were 3 head-to-head comparisons. Baseline characteristics of populations varied
across studies. None of the trials enrolled patients whose symptoms were poorly controlled with
medical therapy.

Open fundoplication vs. non-PPIs in patients with complicated GERD: At 10-year followup
(PPIs were used by most patients in a nonstandardized fashion during the followup period), surgical
patients had better symptom score when taken off antireflux medications compared to medical patients;
less bodily pain; no difference in esophagitis grade; 2/3 of surgical patients were on medications.
(Comment: observational and comparative surgical studies reported 90% of patients were off
antireflux medications at >= 5 years followup.)

Open fundoplication vs. omeprazole in patients with
GERD but without complications: At 5-year followup, there was less treatment failure in surgical
group, but no significant difference if dose of omeprazole was adjusted in cases of relapse.

Conclusion: Fundoplication was as effective as medical treatments for relief of GERD
symptoms and decreasing esophageal acid exposure, at least for up to 2 years of followup. There was
no difference in the outcome of esophagitis. The proportion of patients freed from long-term
antireflux medications is unclear.

Surgical vs. endoscopic

Weak

There was no head-to-head comparison for the 2 treatments.

In nonrandomized studies, more patients treated with laparoscopic fundoplication were
satisfied with their results compared with those who had endoscopic therapies.